Oxandrolone (i.e., 17β-hydroxy-17α-methyl-2-oxa-5α-androstan-3-one) is a known anabolic steroid that has various therapeutic uses. Methods of producing oxandrolone are known. For example, U.S. Pat. No. 3,109,016 discloses a process of manufacture of 17-oxygenated 2-oxa-5α-androstan-3-ones. The '016 patent discloses the reaction of 17β-hydroxy-17α-methyl-5α-androst-1-en-3-one in methylene chloride and methanol with ozone to produce methyl 17β-hydroxy-17α-methyl-1-oxo-1,2,-seco-A-nor-5α-androstan-2-oate and, alternatively, with ozone in methylene chloride to yield 17β-hydroxy-17α-methyl-1-oxo-1,2,-seco-A-nor-5α-androstan-2-oic formic anhydride. According to the '016 patent, the 1,2-seco intermediates are converted to the corresponding anabolic 2-oxa compound by treatment with a reducing agent in aqueous medium. The methyl 17β-hydroxy-17α-methyl-1-oxo-1,2,-seco-A-nor-5α-androstan-2-oate may be contacted with sodium borohydride in aqueous sodium hydroxide to form 17β-hydroxy-17α-methyl-2-oxa-5α-androstan-3-one (i.e., oxandrolone).
U.S. Pat. No. 3,128,283, which relates to 17-oxygenated androstane and estrane derivatives in which the A ring contains a lactone structure, also discloses an example of the production of oxandrolone. 17β-hydroxy-17α-methyl-5α-androst-1-en-3-one is reacted in aqueous acetic acid with osmium tetroxide and lead tetracetate to afford 17β-hydroxy-17α-methyl-1-oxo-1,2,-seco-A-nor-5α-androstan-2-oic acid. This compound is converted to 17β-hydroxy-17α-methyl-2-oxa-5α-androstan-3-one by reduction with sodium borohydride in aqueous sodium hydroxide. A disadvantage of methods that use lead tetracetate, however, is that lead tetracetate is a highly toxic compound.
17-hydroxy-17-methyl-5-androst-1-en-3-one may be formed from 17-hydroxy-17-methyl-5-androstan-3-one. For example, U.S. Pat. No. 2,260,328 discloses mixing 17-hydroxy-17-methyl-5-androstan-3-one in glacial acetic acid solution with bromine. This product is precipitated and purified. The product is then heated with dimethylaniline or potassium acetate in glacial acetic acid under pressure to eliminate hydrogen bromide, thus forming 17-hydroxy-17-methyl-5-androst-1-en-3-one.
Methods using bromination-dehydrobromination are disadvantageous due to low yields. For example, these methods typically generate the compound in a 15-30% overall yield with the compound being contaminated in approximately 5–10% of methyl testosterone. Such methods generally require the use of chromatography such as silica gel chromatography to obtain pure product.
It would be advantageous to provide a process for producing oxandrolone that results in the formation of oxandrolone in relatively high yields and purity.